Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make?

Abstract

BackgroundShivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever above 40°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol to manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%).MethodsFrom February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine whether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (≥40°C). Rates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in Ecuador following PPH treatment with 800mcg sublingual misoprostol.ResultsThe 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50; 16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the 600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases of delirium/altered sensorium were reported with the 600mcg dose and women’s assessment of severity/tolerability of shivering and fever was better with the lower dose.Conclusions600mcg sublingual misoprostol was found to decrease the occurrence of high fever among Ecuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this treatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other populations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following sublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger trials to confirm the efficacy of lower dosages may be justified.Trial RegistrationClinical trials.gov, Registry No. NCT01080846

A crossover pharmacokinetic study of misoprostol by the oral, sublingual and buccal routes

“…However, no serious adverse events were seen in this trial. Fever, a dose-and routerelated side effect, [10] was not noted in this population. Some women dropped out of the study due to side effects; however, women who require the medication for an obstetric indication may tolerate side effects differently.…”

Severe morbidity with sublingual misoprostol in a post-partum patient: a case report

“…In all these cases, there was history of misoprostol administration via oral, sublingual or rectal route. 3,4,12,13 However, no direct relation with misoprostol administration could be established in these cases. Nonetheless, these findings do point out that misoprostol may have unexplained adverse effects on homeostatic mechanisms specifically thermoregulation of the body, especially during pregnant and post-partum phase.…”

Misoprostol-Induced Fever and Genetic Polymorphisms in Drug Transporters SLCO1B1 and ABCC4 in Women of Latin American and European Ancestry

“…Demographic data for patients from Ecuador have been reported previously [17]. Self-reported ethnicity for women in Ecuador included 88% (44/50) mestiza, 2% (1/50) indigenous, 2% (1/50) black, 4% (2/50) mulata and 4% (2/50) white.…”

“…Participants from Ecuador were recruited at Hospital Gineco-Obstétrico Isidro Ayora, in Quito, and their demographic characteristics have been published previously [17]. Briefly, of a total of 727 women screened for PPH, 6.9% (50/727) were diagnosed with PPH due to atonic uterus and were administered 600 mcg of sublingual misoprostol.…”

“…Body temperature can reach over 40°C in some women [14][15][16], with the peak occurring at 90 min [13,17]. The incidence of fever depends on gestational age of pregnancy (e.g.…”